About

Aalim M. Weljie joined the faculty of the University of Pennsylvania in May 2012 after relocating from the University of Calgary (Alberta, Canada). His research interests include circadian and sleep metabolomics; clinical and diagnostic metabolic profiling with specific applications to cancer; metabolomics applications to environmental toxicology; and the development of state-of-the-art metabolomics technologies and protocols with nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography – mass spectrometry (LC-MS) with clinical and translational research applications.

Research topics

• Biochemistry
• Cell biology
• Biology
• Medicine
• Cancer research
• Internal medicine
• Genetics
• Pathology
• Endocrinology
• Chemistry
• Gastroenterology

Selected publications

• Glucose is dynamically regulated by time of day in humans and Drosophila

  PLoS Biology · 2026-04-16 · 1 citations

  articleOpen accessSenior author

  Biological clocks shape metabolism, but how circadian programs govern nutrient processing is unclear. Here, using human metabolomics and 13C6-glucose tracing in Drosophila, we delineate previously under characterized daily oscillations in glucose-derived metabolic networks, providing a mechanistic framework for a purpose-built isotope-tracing approach. In flies, we reveal a pronounced "rush hour" of glucose utilization early in the light phase, with carbons directed to biosynthetic and energetic pathways. By contrast, a dopamine reuptake-deficient hyperactive mutant (fumin) with elevated metabolic rate shows phase-shifted and amplified metabolic peaks, indicating that altered neural signaling reshapes temporal glucose flux. Neither altered feeding schedules nor short-term fasting disrupt these intrinsic metabolic rhythms, strongly suggesting that circadian timing, rather than nutrient availability, orchestrates temporal homeostasis. By integrating human metabolite profiling with isotope-tracing in flies, we define a conserved temporal architecture of glucose utilization and demonstrate that metabolic flux is dynamically gated across the day. Our findings establish a framework for understanding how circadian misalignment contributes to metabolic dysfunction and disease.

  PublisherDOI

• Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism

  UNC Libraries · 2026-01-14

  articleOpen access
  PublisherDOI

• Age and the Diurnal Oscillatory Features of the Human Chronobiome

  medRxiv · 2026-01-23 · 2 citations

  article

  The molecular clock regulates diverse aspects of human biology. As people age, diurnal rhythms deteriorate, most evidently in the daytime napping and nighttime waking of older individuals. To understand how temporal deconsolidation of oscillatory networks could contribute to age-related disease expression, we studied the chronobiome at unprecedented depth in young and old apparently healthy individuals. Transomic integration segregated age groups and identified candidate mechanisms by which oscillatory function might contribute to age dependent distinctions. In an orthogonal approach, we validated as true cyclers many proteins identified in the UK Biobank as predictors of health and disease outcomes. Here, age-specific alterations in the cycling proteome across disease phenotypes is consistent with our hypothesis that deconsolidated circadian programs associate with increased susceptibility to age-related disease.

  PublisherDOI

• Peripheral metabolic dysfunction drives sleep disruption in TDP-43 proteinopathy

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-24 · 1 citations

  articleOpen access

  Abstract Sleep disruption is an early and prevalent feature of neurodegenerative disease, commonly attributed to neuronal circuit dysfunction or cell loss. However, sleep is tightly coupled to metabolic state, raising the possibility that systemic metabolic abnormalities contribute to disease-associated sleep phenotypes. Using Drosophila models of TDP-43 proteinopathy, we investigated whether peripheral metabolic dysfunction plays a causal role in sleep disruption. We show that TDP-43 expression induces a chronic, starvation-like metabolic state characterized by depletion of peripheral carbohydrate stores despite normal feeding. Restoration of sleep fails to correct these metabolic defects, whereas improving peripheral metabolic state robustly rescues sleep. A modifier screen of ∼650 RNAi lines identified Salt-inducible kinase 3 (SIK3) as a potent suppressor of both sleep loss and starvation sensitivity. Transcriptomic and spatial metabolomic analyses reveal that SIK3 selectively remodels a peripheral metabolic program centered on the pentose phosphate pathway and redox-associated metabolites without globally restoring energy stores. Together, these findings identify systemic metabolic dysfunction as a key driver of sleep disruption in TDP-43 proteinopathy and highlight peripheral metabolism as a potential therapeutic entry point for sleep dysfunction in neurodegenerative disease.

  PublisherDOI

• Locoregional lactate dehydrogenase inhibition potentiates therapy and overcomes treatment resistance in hepatocellular carcinoma

  Hepatology · 2026-04-30

  article

  BACKGROUND AIMS: Metabolic inhibitors have demonstrated limited efficacy for cancer therapy due to metabolic plasticity and systemic toxicity. Locoregional therapies (LRT), such as transarterial embolization (TAE) or transarterial chemoembolization (TACE), generate ischemic stress that reprograms the tumor microenvironment (TME) toward glycolytic dependency, creating an opportunity to sensitize hepatocellular carcinoma (HCC) to metabolic inhibition. This study investigated whether pharmacologic inhibition of lactate dehydrogenase (LDH) with NCATS-SM1441 could exploit TAE-induced metabolic vulnerabilities to improve therapeutic efficacy in HCC. APPROACH RESULTS: Human HCC cell lines were exposed to replete or ischemic (TAE-like) conditions and treated with the LDH inhibitor NCATS-SM1441. Glucose/lactate flux, adenosine triphosphate (ATP) levels, and viability were assessed. In vivo, a diethylnitrosamine (DEN)-induced rat HCC model was treated with intraarterial NCATS-SM1441, TAE, or their combination. Drug distribution, tumor metabolism, necrosis, and survival were analyzed using mass spectrometry imaging, histopathology, T2-weighted magnetic resonance imaging (MRI), and survival metrics. Ischemic conditions induced LDHA expression and glycolytic flux, enhancing susceptibility to LDH inhibition. The combination of intraarterial NCATS-SM1441 before embolization increased intratumoral drug accumulation, reduced systemic exposure, and synergized with TAE to suppress lactate production, promote tumor necrosis, and significantly extend local progression-free survival. CONCLUSIONS: TAE conditions the TME to create a therapeutically targetable glycolytic dependency. Combining TAE with LDH inhibition overcomes key limitations of metabolic inhibitors as monotherapies, enhancing local control and survival with minimal systemic toxicity, supporting integration of metabolism-targeted agents with LRT for unresectable HCC.

  PublisherDOI

• Integrated Respirometry and Metabolomics Unveil Circadian Metabolic Dynamics in Drosophila

  eLife · 2025-11-04

  articleOpen accessSenior author

  Precise temporal regulation of metabolism by sleep and circadian rhythms is essential for dynamic energy homeostasis, yet the link between systemic metabolism and respiratory demands remains poorly defined. We combined high-resolution respirometry with LC-MS-based metabolomics to characterize respiratory dynamics and metabolic states in Drosophila melanogaster to uncover genotype-specific impacts of sleep and circadian disruption. Wild-type flies under light-dark cycles (WT-LD) showed rhythmic respiratory patterns reflective of anticipatory coordination of mitochondrial energy metabolism, amino acid turnover, and redox cycling. In contrast, short-sleep mutants (fmn, sss) exhibited elevated metabolic rates and reactive shifts of fuel preferences toward lipid and amino acid catabolism and displayed signs of mitochondrial stress. Circadian-clock disrupted flies (per01, WT-DD) showed reactive and widespread metabolic dysregulation and impaired redox homeostasis. These findings demonstrate that both sleep and circadian systems are essential for aligning metabolic substrate selection with energy demands, offering mechanistic insights into how disruptions in behavioral states compromise metabolic health.

  PublisherDOI

• Integrated Respirometry and Metabolomics Unveil Circadian Metabolic Dynamics in Drosophila

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-25

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Precise temporal regulation of metabolism by sleep and circadian rhythms is essential for dynamic energy homeostasis, yet the link between systemic metabolism and respiratory demands remains poorly defined. We combined high-resolution respirometry with LC-MS-based metabolomics to characterize respiratory dynamics and metabolic states in Drosophila melanogaster to uncover genotype-specific impacts of sleep and circadian disruption. Wild-type flies under light-dark cycles (WT-LD) showed rhythmic respiratory patterns reflective of anticipatory coordination of mitochondrial energy metabolism, amino acid turnover, and redox cycling. In contrast, short-sleep mutants ( fmn , sss ) exhibited elevated metabolic rates and reactive shifts of fuel preferences toward lipid and amino acid catabolism and displayed signs of mitochondrial stress. Circadian-clock disrupted flies ( per 01 , WT-DD) showed reactive and widespread metabolic dysregulation and impaired redox homeostasis. These findings demonstrate that both sleep and circadian systems are essential for aligning metabolic substrate selection with energy demands, offering mechanistic insights into how disruptions in behavioral states compromise metabolic health.

  PublisherOA PDFDOI

• Integrated Respirometry and Metabolomics Unveil Circadian Metabolic Dynamics in Drosophila

  eLife · 2025-11-04 · 1 citations

  articleOpen accessSenior author

  Precise temporal regulation of metabolism by sleep and circadian rhythms is essential for dynamic energy homeostasis, yet the link between systemic metabolism and respiratory demands remains poorly defined. We combined high-resolution respirometry with LC-MS-based metabolomics to characterize respiratory dynamics and metabolic states in Drosophila melanogaster to uncover genotype-specific impacts of sleep and circadian disruption. Wild-type flies under light-dark cycles (WT-LD) showed rhythmic respiratory patterns reflective of anticipatory coordination of mitochondrial energy metabolism, amino acid turnover, and redox cycling. In contrast, short-sleep mutants (fmn, sss) exhibited elevated metabolic rates and reactive shifts of fuel preferences toward lipid and amino acid catabolism and displayed signs of mitochondrial stress. Circadian-clock disrupted flies (per01, WT-DD) showed reactive and widespread metabolic dysregulation and impaired redox homeostasis. These findings demonstrate that both sleep and circadian systems are essential for aligning metabolic substrate selection with energy demands, offering mechanistic insights into how disruptions in behavioral states compromise metabolic health.

  PublisherDOI

• Author response: Integrated Respirometry and Metabolomics Unveil Circadian Metabolic Dynamics in Drosophila

  2025-11-04

  peer-reviewOpen accessSenior author

  Precise temporal regulation of metabolism by sleep and circadian rhythms is essential for dynamic energy homeostasis, yet the link between systemic metabolism and respiratory demands remains poorly defined. We combined high-resolution respirometry with LC-MS-based metabolomics to characterize respiratory dynamics and metabolic states in Drosophila melanogaster to uncover genotype-specific impacts of sleep and circadian disruption. Wild-type flies under light-dark cycles (WT-LD) showed rhythmic respiratory patterns reflective of anticipatory coordination of mitochondrial energy metabolism, amino acid turnover, and redox cycling. In contrast, short-sleep mutants (fmn, sss) exhibited elevated metabolic rates and reactive shifts of fuel preferences toward lipid and amino acid catabolism and displayed signs of mitochondrial stress. Circadian-clock disrupted flies (per01, WT-DD) showed reactive and widespread metabolic dysregulation and impaired redox homeostasis. These findings demonstrate that both sleep and circadian systems are essential for aligning metabolic substrate selection with energy demands, offering mechanistic insights into how disruptions in behavioral states compromise metabolic health.

  PublisherDOI

• Multimodal landscape of atherosclerotic plaques: A spatial omics approach with mass spectrometry imaging

  Analytica Chimica Acta · 2025-09-28 · 3 citations

  articleOpen access

  Atherosclerotic plaques are complex and heterogeneous structures, originating as fatty streaks in the vasculature and formed by the accumulation of lipids and foam cells. Over time, these lesions progress as inflammation, smooth muscle cell proliferation and phenotypic switching, and extracellular matrix deposition contribute to plaque growth, culminating in their fracture, reactive thrombogenesis, and a cardiovascular event such as myocardial infarction and stroke. Traditional bulk mass spectrometry (MS) analysis has yielded critical insights into the molecular mechanisms of plaque formation and disease progression, but it is unable to determine the spatial heterogeneity and microenvironmental complexity within the lesion. Recent advances in mass spectrometry imaging (MSI) based omics, including spatial lipidomics, proteomics, and metabolomics, have enabled unprecedented visualization of molecular distribution in atherosclerotic plaques at cellular resolution. These techniques promise to elucidate the distinct cellular crosstalk, lesion vulnerability, and sex-specific disease mechanisms that contribute to plaque development and rupture. This review examines the recent advances in MS-based spatial omics and their application to atherosclerotic plaques in both experimental models and human samples. We highlight recent findings, explore their implications for precision medicine and translational research, and discuss current challenges in sample preparation and data integration. Despite challenges, we suggest approaches for integration of MS-based spatial omics using artificial intelligence (AI) to enhance data integration, interpretation, and translational applications in atherosclerosis research. These advances promise to broaden our understanding of atherosclerosis and identify novel therapeutic targets to limit the burden of cardiovascular disease. Overview of the spatial omics workflows using mass spectrometery imaging. • MSI is a powerful technique that enables spatially resolved mapping of lipids and proteins in atherosclerotic plaques. • MSI is a tool to investigate region specific alterations in atherosclerotic plaques. • Challenges to achive cellular and sub-cellular resolution in MSI • Multimodal approaches will enhance insights into disease progression and plaque vulnerability. • High-throughput annotation and machine learning-based data integration tools need further development.

  PublisherDOI

Recent grants

• Balance of sleep and circadian metabolic switches in Drosophila

  NIH · $2.1M · 2019–2024

• Forgetting to sleep: metabolic consequences of sleep loss and associated neurocognitive deficits

  NIH · $443k · 2017–2021

• Project 2- The ISR effector ATF4 in metabolic reprogramming and survival during Myc-induced tumorigenesis

  NIH · $21.7M · 2013–2025

• Determining and enhancing metabolite fitness for metabolomics measurements

  NIH · $626k · 2017–2020

Frequent coauthors

• Arjun Sengupta

  California University of Pennsylvania

  106 shared

• Hans J. Vogel

  Helmholtz Centre for Environmental Research

  74 shared

• Seth D. Rhoades

  Translational Therapeutics (United States)

  67 shared

• Brian J. Altman

  University of Rochester

  63 shared

• Saikumari Krishnaiah

  49 shared

• Chi V. Dang

  University of Toronto

  48 shared

• Annie L. Hsieh

  Massachusetts General Hospital

  42 shared

• Amita Sehgal

  University of Pennsylvania

  39 shared

Labs

• Weljie LabPI

  Our lab is at the forefront of metabolomics technologies to examine biological problems in a translational medicine context. Our focus is on developing analytical methods to advance research in translational medicine.

Education

• B.S., Chemistry; Certificate in Engineering

  Mount Allison University

  1996

• Ph.D., Biochemistry

  University of Calgary

  2002